DESCRIPTION (Adapted from the application) The role of cell biology in gastrointestinal research continues to increase. The formation of the new Cell Biology & Signaling Core reflects the scientific needs of the Center's, as well as its changing constituency. Core facilities in cell biology were first made available when Dr. Stanley Fallow joined the Center that resulted in the renaming of the Genetic Engineering Core to the Molecular and Cellular Biology Core. Standard transmission microscopy was the major Cell Biology offering at that time. Cell biology now represents the major research focus of many DDRCC research base investigators and includes Cartwright, Cooper, Kim, Lowe, Mochly-Rosen, Nelson, Omary, Sibley, and Triadafilopoulos. The work of these investigators provides the Center with expertise in sorting proteins to specific intracellular sites, epithelial polarity, cell adhesion, signal transduction, and the cytoskeleton. An emerging theme in tissue biology is understanding how multiple signals are integrated in the development, differentiation, and function of different cell types within the tissue, and the events that lead to the development of disease states. The ability of cells to respond to these signaling events involves the formation and integration of many signaling cascades. In the past, these signaling cascades were assumed to be separate albeit parallel, but it is now clear that they are part of dynamic networks. To identify the molecular basis for tissue responses in normal and disease states, we need to be able to investigate selective protein-protein interactions, the sorting of protein complexes to specific intracellular sites in polarized intestinal cells, and protein phosphorylation/dephosphorylation events. Clearly, no one lab has the sufficient expertise to address all of these signaling events. In recognition of this, we constructed the new Cell Biology & Signaling Core Facility to provide members of the DDRCC with access to the necessary cutting edge expertise in this area. The Core will provide both technical expertise in the design and implementation of experiments in these areas (Service), as well as ongoing advice (troubleshooting) during the performance of the experiments. Although some of us are geographically separated, our publication record demonstrates that this has not inhibited us in the past from extensive and productive collaborations.